Oral submucous fibrosis is a pre-cancerous condition of oral cancer, but not an oral cancer. The primary features of oral submucous fibrosis are the inflammation and fibrosis of the oral submucosal tissue and deeper connective tissue. If the therapy for oral submucous fibrosis is not started immediately, the oral submucous fibrosis may develop into oral cancer.
There are epidemiological studies indicating that chewing areca nuts is the primary cause of oral submucous fibrosis. The lesions usually present in the buccal mucosa and secondarily present in the palatal portion and retromolar trigone. At first, the affected mucosa is blanched, and then, ulcers and blisters will appear repeatedly. Eventually, the mucosa will lose elasticity, and thus, may lead to a difficulty for patients to open their mouths wide that would seriously affect daily functions of mouths such as eating, teeth brushing, oral exams, and oral therapies. If the lesion occurs in the soft palate of oropharynx, it may cause dysphagia, uvula atrophy or uvula deformity. Patients of oral submucous fibrosis usually have a feeling of burning, stabbing pain and dryness, and are extremely sensitive to spicy and hot foods, but have a reduced gustatory sensation.
Currently, there is no drug that can prevent and/or treat oral submucous fibrosis effectively. Therapies of oral submucous fibrosis usually rely on the steroid injections to reduce the content of collagen in the oral submucosal tissue, or rely on the traditional surgery or laser surgery to excise the affected tissues. However, steroid injections can only alleviate the symptoms and cannot cure the oral submucous fibrosis. There are side effects such as moon face, obesity, buffalo hump, osteoporosis, skin thinning, edema, susceptibility to infection, acne, retardation of height, increased blood sugar, increased infection rate, oral fungal infection, increased body hair and impaired wound healing. Furthermore, the excision of a large tissue lesion via traditional surgery or laser surgery may easily lead to wound contraction and scar formation during wound healing, and thus needs to take the issues such as the limitations of opening mouths and facial appearance into consideration. In this respect, oral surgeons would consider skin grafts as the remedial measure, but the skin grafts may hide early relapses. In addition, as treating older patients or patients having large lesions with traditional surgery or laser surgery, both the surgical damages and patients' immunity and life quality will be considered.
In view of the above issues regarding the therapies of oral submucous fibrosis, pharmaceutical researchers are dedicated to developing drugs which can prevent and/or treat oral submucous fibrosis. Inventors of the present invention discovered that butylidenephthalide is effective in inhibiting the epithelial-mesenchymal transition (EMT) of oral submucosal tissue cells, inhibiting oral submucosal tissue cells to differentiate into myofibroblasts, and inhibiting the activation of myofibroblasts, and thus, can inhibit the accumulation of collagen in oral submucosal tissue, inhibit the contraction of extracellular matrix in oral submucosal tissue, and be used to provide drugs that can prevent and/or treat oral submucous fibrosis.